Joshua Trachtenberg, graduated from Brandeis in 1990 and is a leader in studying the living brain in action using advanced imaging technology. After establishing his research laboratory at UCLA, he founded a company – Neurolabware – in order to build the sophisticated custom research microscopes that are needed to perform groundbreaking work in understanding how the brain develops and how diseases and injuries interrupt its normal functioning. His company is created by scientists and for scientists, and is unique in creating high quality microscopes that are easy to use but also have the flexibility to be used in creative ways in innovative experiments, and in combination with a variety of other devices.

Brandeis University is now seeking to acquire one of these advanced microscopes that can observe fundamental processes inside the living brains of animals engaged in advanced behaviors. The reasonant scanning two-photon microscope from Neurolabware allows researchers to understand and image large networks of neurons in order to visualize which cells and networks are involved with specific memories or how these processes go awry in disease. “This approach is unparalleled. There is no other technique around that could possibly touch this,” Trachtenberg says.

Previous two-photon technologies permitted only very slow imaging, allowing scientists to take a picture about every two seconds, but the resonant two-photon technology is a major breakthrough that allows scientists to take pictures at about 30 frames per second. This speed increase is a major game changer. Not only can one observe activity in the brain at a higher speed, but it is possible to take pictures at a speed that is faster than the movement artifacts that must be accounted for, such as breathing or heart beats. Because one can see the movement, it can be corrected, allowing high resolution functional imaging of structures as small as single synaptic spines in the living brain. Further, advances in laser technology and fluorescent labels now allow scientists to see deeper into the brain than ever before, compounding the recent advantages of increased speed.

The brain has a remarkable capacity to record our daily experiences and recall this stored information to guide our behavior. For example, every time you decide to get a cup of coffee on campus, you immediately know where to go and then step toward your destination. The ability to successfully memorize paths and navigate in the environment is fundamental for animals searching for food (see Illustration), as well as for humans surviving in a complicated environment, especially when you don’t have your smartphone to rely on, but only your brain as the inner GPS! However, how does the brain learn and remember such plans that allow us to get from one place to another?

We know that a structure in brain called the hippocampus plays an important role in encoding and storing memories. The hippocampus is thought to replay remembered experiences during fast, ripple-like brain waves, termed sharp-wave ripples (SWRs), that occur during “down-time” for the brain, i.e., offline periods during sleep and during pauses in active behavior. It has been previously shown by Jadhav and colleagues that selectively disrupting these ripple oscillations using precisely-timed electrical impulses impairs the ability of animals to learn in spatial mazes, suggesting that this “mental replay” is important for navigation and memory (Jadhav et al., 2012, Science). Notably, mental replay is not isolated activity in the hippocampus, but works together with the prefrontal cortex (PFC), the executive center of brain involved in storing memories and making decisions (Jadhav et al., 2016, Neuron). However, exactly how such memory replay supports memory processing in waking and sleep states had remained elusive.

In a new article published in the Journal of Neuroscience (Tang et al., 2017), the Jadhav lab (the team included Neuroscience graduate students Wenbo Tang and Justin Shin) used high-density electrophysiology to record large numbers of neurons in both the hippocampus and prefrontal cortex in both sleep and awake states. They discovered that as rats learned a spatial memory task, the activity in the hippocampal-prefrontal network replayed recent experiences in a precise manner during SWRs that occurred when animals paused from actively exploring the maze. This structured mental replay related to ongoing spatial behavior is ideally suited for storing and retrieving memories to inform decisions. When animals were asleep after exploring the maze, the hippocampal-prefrontal replay, however, appeared “noisy” and mixed. This replay occurring during sleep periods can support the ability of the brain to consolidate memories, by selectively integrating related memories to build a coherent map for long-term storage (see Illustration). These findings show how memory information is communicated between the hippocampus and PFC during ripple oscillations, and indicate that mental replay during sleep and awake states serve distinct roles in memory. These studies collectively provide fundamental knowledge about the neural substrates of memories. They will thus provide important insights into memory deficits that are prevalent in many neurological disorders that involve the hippocampal-prefrontal network, such as Alzheimer’s disease and schizophrenia.

investigate the physiological interactions between the brain’s hippocampal and prefrontal cortex regions that support learning and memory-guided behavior. The two structures are important for different aspects of memory formation, storage, and retrieval, and impaired hippocampal-prefrontal interactions have been implicated in neurological disorders related to cognition, including memory disorders and schizophrenia.